In 1997, the US Food and Drug Administration approved for sale the first recombinant human platelet-derived growth factor (rhPDGF) for treatment of human non-healing wounds. The product is marketed by Ortho-McNeil pharmaceutical and has been approved for use in ulcers of lower-extremity diabetic neuropathy by application of a gel vehicle to promote granulation of wound bed. However, the FDA-approved rhPDGF showed only a 10% efficacy for the patients. There appears to be much room left for improvement.
The venom of the Australian taipan snake, Oxyuranus s. scutellatus, contains taipoxin, an abundantly lethal neurotoxin, which has a component, β-taipoxin, which has mitogenic properties. (The intact complex molecule of taipoxin has a molecular weight 45.6 kDa and is composed of alpha (α), beta (β) and gamma (γ) subunits.) Lind reported that the amino acid sequence of the β-taipoxin subunit consisted of 118 amino acids (Lind, P. and Eaker D. (1982). Amino-acid sequence of the β1 Isosubunit of Taipoxin, an Extremely Potent Presynaptic Neurotoxin from the Australian snake Taipan (Oxyuranus s. scutellatus). Eur. J. Biochem. 124:441–443). Lipps reports a partial amino sequence for beta taipoxin and reports that it has utility to promote cell growth in vitro and in the treatment of wounds. (Lipps, B. V., “Beta Taipoxin As A Cell Growth Factor and Method” published PCT application number WO 95/29987, 9 Nov. 1995; see also Lipps, B. V. (2000) ″Isolation of subunits, α, β and γ of the complex taipoxin from the venom of Australian taipan snake (Oxyuranus s. scutellatus): characterization of β-taipoxin as a potent mitogen.
Toxicon 38: 1–11). However, for a number of reasons, it may prove not to be commercially viable to use taipan snake venom as a natural source for a wound healing product.
It is an object of this invention to provide a peptide which mimics the neurotrophic, keratinocytic and wound healing properties of β-taipoxin, but which is synthetic, rather than derived from venom.
It is another object of the invention is to provide a synthetic peptide which is short enough to be made in cost-effective abundance to provide a highly effective therapeutic for healing wounds and burns and a highly effective growth promoter for the growth of eukaryotic cells in serum-free medium.
It is a further object to provide a treatment for wounds (traumatic, internal, superficial, decubitus ulcers, burns, etc.) by suitable administration of a synthetic peptide to wound area.